Off-label tirzepatide use in overweight adults with type 1 diabetes produced 23% weight loss, improved cardiovascular markers, and preserved kidney function over 21 months — benefits that persisted even after accounting for weight loss.
-59 lbs (23.4%) weight lossOverweight adults with type 1 diabetes using tirzepatide for 21 months, with cardiovascular and kidney benefits independent of weight change
What the researchers found
Over 21 months, 84 overweight/obese adults with type 1 diabetes using tirzepatide off-label lost an average of 59 pounds (23.4% body weight), while matched controls gained 1.7 pounds. HbA1c dropped 0.50% more in tirzepatide users versus controls. Beyond weight and blood sugar, tirzepatide significantly improved total cholesterol, LDL, triglycerides, systolic blood pressure, and preserved kidney function (eGFR).
Remarkably, the cardiovascular and kidney benefits remained statistically significant even after adjusting for weight loss and HbA1c changes — suggesting tirzepatide has direct protective effects on the heart and kidneys independent of its metabolic benefits. Controls saw significant eGFR decline over the same period.
Why it matters
This is among the first long-term real-world data on tirzepatide use in type 1 diabetes, where it is not approved. Nearly two-thirds of adults with T1D are now overweight or obese, contributing to cardiovascular disease and kidney problems — yet they have few drug options beyond insulin. The finding that tirzepatide produced 23% weight loss, improved cardiovascular biomarkers, and preserved kidney function independently of metabolic improvements makes a compelling case for formal clinical trials.
The numbers in context
n=84 tirzepatide, n=38 controls · Weight loss: -59 lbs (-23.4%) vs +1.7 lbs · HbA1c: -0.50% vs -0.24% (p=0.017) · Improved: LDL, total cholesterol, triglycerides, systolic BP · eGFR preserved in tirzepatide, declined in controls · Duration: 21 months · Baseline BMI: 35.2 vs 33.3
How the study worked
Retrospective chart review of 84 overweight/obese adults with T1D prescribed tirzepatide since July 2022 (minimum 6 months use) at a university hospital. Controls (n=38) were frequency-matched for age, diabetes duration, sex, HbA1c, and BMI. Data from electronic medical records over 21 months. Linear mixed effects models examined changes in lipids, blood pressure, and eGFR over time, including models adjusted for weight and HbA1c changes.
Who was studied
122 overweight/obese adults with type 1 diabetes (84 on tirzepatide, 38 matched controls) at a university hospital
What this study cannot tell us
Retrospective observational design — not a randomized controlled trial, so confounding factors may explain some results. Tirzepatide users may have been more motivated or had different healthcare utilization patterns. Relatively small sample (84 + 38 controls) from a single center. Off-label prescribing means dosing may have varied. The study cannot prove causation for the weight-independent cardiovascular and kidney benefits.
How to read the evidence
This is a retrospective observational study with matched controls from a single center. While it provides valuable long-term real-world data, the lack of randomization and relatively small sample size limit the ability to draw causal conclusions. The authors appropriately call for a formal RCT.
When this study was published
Published in 2025 with data through early 2024, this is among the first long-term real-world reports of tirzepatide use in type 1 diabetes. It reflects current clinical practice where off-label prescribing is occurring ahead of formal trials.
The bigger picture
Tirzepatide (Mounjaro/Zepbound) is approved for type 2 diabetes and obesity but not type 1. This study adds to growing evidence that dual-incretin agonists may have a role in T1D, where obesity is increasingly common but treatment options are limited to insulin alone. The weight-independent cardiovascular and kidney benefits mirror findings in T2D studies and support the theory that GLP-1/GIP signaling has direct cardioprotective and nephroprotective effects. The authors call for a formal RCT.
Questions still open
- Would a randomized controlled trial of tirzepatide in T1D confirm these cardiovascular and kidney benefits?
- What is the optimal tirzepatide dose in type 1 diabetes, and how should insulin regimens be adjusted?
- Are the weight-independent organ benefits driven by GLP-1 signaling, GIP signaling, or both?
Common questions
Is tirzepatide approved for type 1 diabetes?
How can heart and kidney benefits be independent of weight loss?
Read the original research
Cardiovascular and Renal Biomarkers in Overweight and Obese Adults with Type 1 Diabetes Treated with Tirzepatide for 21 Months.
Diabetes technology & therapeutics, 27(3), 152-160
Citation
Garg, Satish K; Kaur, Gurleen; Renner, Drew; Lanning, Monica S; Mason, Emma; Beatson, Christie; Ciesco, Kelly; Snell-Bergeon, Janet. (2025). Cardiovascular and Renal Biomarkers in Overweight and Obese Adults with Type 1 Diabetes Treated with Tirzepatide for 21 Months.. Diabetes technology & therapeutics, 27(3), 152-160. https://doi.org/10.1089/dia.2024.0481